BACKGROUND:LncRNA-TNFRSF13C,an important factor in B cell development and function,is expressed in periodontal tissues of patients with periodontitis,but the specific mechanism is still unclear. OBJECTIVE:To investigate the mechanism of lncRNA-TNFRSF13C regulating miR-1246 on hypoxia-inducible factor 1α in periodontal cells. METHODS:Human periodontal ligament cells(hPDLCs)were treated with lipopolysaccharide and divided into group A(hPDLCs cell lines without transfection),group B(hPDLCs cell lines transfected with TNFRSF13C NC-siRNA),group C(hPDLCs cell lines transfected with TNFRSF13C-siRNA),group D(hPDLCs cell line transfected with miR-1246 mimics),group E(hPDLCs cell line transfected with miR-1246 siRNA),group F(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 mimics),and group G(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 siRNA).The relative expression of lncRNA-TNFRSF13C and miR-1246 in each group was detected by qRT-PCR.Cell counting kit-8 assay was used to detect cell viability.Apoptosis was detected by flow cytometry.Expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins was detected by western blot.The correlation between lncRNA-TNFRSF13C and miR-1246 was analyzed by Pearson,and the targeting relationship was analyzed by dual-luciferase reporter assay. RESULTS AND CONCLUSION:There was no significant difference in human periodontal ligament cell activity,apoptosis rate and protein indexes between groups A and B(P>0.05).Compared with group B,hPDLCS cell activity in group C was increased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were decreased(P<0.05).Compared with group C,hPDLCS cell activity in group D was decreased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were increased(P<0.05).Compared with group D,the cell activity of group E was increased(P<0.05).The cell activity in group F was lower than that in group E,and the apoptosis rate was reduced in both groups E and F(P<0.05).Compared with group F,the cell activity of group G was increased,and the apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were decreased(P<0.05).LncRNA-TNFRSF13C was positively correlated with miR-1246(P<0.05).Compared with the TNFRSF13C-siRNA group,the fluorescence activity of miR-1246-wt in the TNFRSF13C-NC group was reduced(P>0.05);compared with the miR-1246-NC group,the fluorescence activities of hypoxia-inducible factor 1α-wt and vascular endothelial growth factor-wt in the miR-1246 mimics group were increased(P<0.05).To conclude,down-regulation of lncRNA-TNFRSF13C can promote the activity of periodontal cells treated with lipopolysaccharide,reduce apoptosis,and inhibit hypoxia-inducible factor 1α and vascular endothelial growth factor.The mechanism is related to the regulation of miR-1246 activity.

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective To investigate the improvement effects of homogeneous fecal microbiota transplantation(FMT)on chemotherapy-induced diarrhea(CID)in mice.Methods Fifteen C57BL/6N mice were divided into control group,CID model group and CID+FMT group according to the random number distribution and remainder grouping method,with 5 mice per group.Control group received no intervention,and their feces were used to prepare fecal bacteria suspension.CID model group was injected intraperitoneally with fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,followed by gavage with 0.1 ml of saline on alternate days.CID+FMT group was given 0.1 ml fecal bacteria suspension gavage on alternate days for one week,followed by intraperitoneal injection of fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,with the experiment ending on the 14th day.During the experiment,the mice's food intake and body weight were recorded.At the end of the experiment,the mice were euthanized with deep carbon dioxide anesthesia,and the mice colonic specimens from cecum to anus were collected for hematoxylin and eosin(HE)staining and histopathological examination.Fecal samples were collected for 16S rRNA gene sequencing.Shannon index,Simpson index and Chao1 algorithm were used to analyze the α-diversity species of the intestinal flora in each group of mice.Similarity analysis(Anosim)was used to perform non-parametric on the inter-group differences of intestinal flora among the mice.Linear discriminate analysis size effect(LEfSe)and nonmetric multidimensional scaling(NMDS)were employed to analyze the intestinal dominant flora and the similarity classification relationships in each group of mice.Results The colonic specimen's length from cecum to anus in CID model group was significantly shorter than that in control group(P<0.05),while there was no significant difference between CID+FMT group and CID model group(P>0.05).The weight of mice in CID model group decreased by 42.04%,while control group mice gained 10.24%,with a significant difference between the two groups(P<0.05).The weight of mice in CID+FMT group decreased by 8.12%,which was significantly improved compared to CID model group(P<0.05).HE staining results revealed the intestinal mucosal structure in CID model group was severely damaged,with atrophy and deformation,accompanied by inflammatory cell infiltration,and the pathological score was higher than that of control group(P<0.05).Compared with CID model group,the intestinal mucosal integrity and crypt cells in the CID+FMT group were improved,with less damage,and the pathological score was lower than that of CID model group,but the difference was not statistically significant(P>0.05).The α-diversity analysis showed that there were significant differences in the Shannon,Simpson and Chao1 indices among the three groups(P<0.05).ANOSIM and NMDS analysis revealed that the intestinal flora in CID+FMT group was closer to the normal intestinal flora compared to CID model group.LEfSe analysis showed that the intestinal flora in CID model group was enriched in famliy_Bacteroidaceae,and the intestinal flora in CID+FMT group was similar to that of control group,with an enrichenment of familiy_Enterobacteriaceae.Conclusion Homogeneous FMT can improve the abundance of intestinal flora in CID mice,making it more similar to normal intestinal flora,thereby protecting intestinal mucosa,reducing damage and alleviating the severity of CID.

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. Conclusion In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Objective To explore the key genes and long non-coding RNAs(lncRNAs)associated with Parkinson's disease(PD).Methods Peripheral blood plasma samples were collected from 6 PD patients and 6 healthy individuals.The mRNA and lncRNA expression profiles were detected using ceRNA microarray technology,and the differentially expressed genes were analyzed using bioinformatics methods.The differentially expressed mRNAs transcribed within 10 kb upstream or downstream of the differentially expressed lncRNAs were defined as potential cis-regulatable(Cis)target genes of the lncRNAs.A PD-specific protein-protein interaction network(PPI)was constructed.Competitive endogenous RNA(ceRNA)networks were also constructed using the differential lncRNAs with mRNAs and known microRNAs.Using MPP+-treated SH-SY5Y cells as a PD cell model,the expressions of the key lncRNAs and their functions were examined.Results We identified 316 genes and 986 lncRNAs showing significant differential expressions in PD patients(P<0.05).The differentially expressed mRNAs and the potential cis-regulatable target genes of these lncRNAs were functionally annotated using GO and KEGG enrichment analysis,and the targeting relationship of the differentially expressed mRNAs and lncRNAs with microRNAs were predicted.Analysis of the ceRNA networks constructed based on the differentially expressed lncRNAs suggested that lnc-MTG2-1:1,lnc-CTSD-5:1,lnc-PCCA-3:1,lnc-VTCN1-3:1,lnc-ZNF25-7:1,and lnc-DAZ3-1:1 might be the key lncRNAs in PD.In MPP+-treated SH-SY5Y cells,the expression of lnc-CTSD-5:1 showed the most significant changes,and silencing lnc-CTSD-5:1 obviously restored the expression level of tyrosine hydroxylase.Conclusion PD patients have significant changes in plasma lncRNA expression profile,and the differentially expressed genes and lncRNAs found in this study may provide new clues for exploring the pathogenesis and identifying potential biomarkers of PD.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

ObjectiveTo systematically analyze international disability data policies and standards, as well as the application of disability data in policymaking, service optimization and inclusive social development, and to clarify the importance of international disability data policies, standard systems and disability data application for the development of disability-related services. MethodsThrough the analysis of policy content and research on the data standard system, this study explored the disability data policy framework, standard system and technical path of data interoperability and integration of international organizations including the United Nations (United Nations Statistics Division and United Nations Children's Fund), World Health Orgnization, United Nations Educational Scientific and Cultural Organization, and International Labour Organization. ResultsInternational organizations established disability data policy frameworks based on their respective mandates, involving data and service development, data standards, data governance, and data application. The international community established a disability data standard system for disability data collection, coding, exchange, interoperability, statistical analysis, data fusion and application. Building a standardized disability data standard system based on the framework of international health classification standards such as International Classification of Functioning, Disability and Health, and International Classification of Diseases, Eleventh Revision would ensure the consistency of cross-national disability data policies, and the interoperability and comparability of disability data, promoting the development of data-driven disability-related services, accurately identifying the service needs of people with disabilities, and optimizing service provision, thereby improving the quality of life and social participation of people with disabilities. ConclusionThe construction and implementation of international disability data policies and data standards have promoted the standardization and interoperability of disability data. With the application of big data, artificial intelligence and blockchain technologies in disability data, international cooperation and cross-industry data fusion in the field of disability data have been promoted, further promoting the development of data-driven disability services, ensuring equal opportunities for people with disabilities to enjoy service resources, and improving the coverage and quality of disability services.

Growth/differentiation factor-5 (GDF-5) belongs to transforming growth factor-β (TGF-β) family, which is expressed in bone, cartilage, heart, brain, kidney, skeletal muscle and tendon, liver, fat and other organs and tissues as well. GDF-5 binds to receptor BMPR-I/BMPR-II and activates different signaling pathways such as smad1/5/8, PI3K/Akt, p38-MAPK. For a long time, numerous studies have shown that GDF-5 plays an important role in protecting joints. However, researchers have found GDF-5 also plays significant biological functions in other organs. For example, GDF-5 improves cardiac function by reducing oxidative stress and fibrosis in infarcted hearts. GDF-5 can also reduce oxidative stress in the brain and increase the number of neurons in effort to delay the progression of Alzheimer’s disease and Parkinson’s disease. It is a situation, research on GDF-5, at present, mainly focuses on the growth and repair of bone, cartilage and tendons, while there are few reports on its biological effects in other organs. Therefore, this article reviews and summarizes the research progress on GDF-5 and metabolic diseases in recent years in order to provide new insights and theoretical basis for the role of GDF-5 in improving metabolic diseases.

Magnetic cell sorting technology is a highly specific and rapid cell sorting technology using superparamagnetic nanocomposites for cell sorting, which is widely used in immunology, stem cytology, oncology, clinical medicine and other fields. Magnetic cell sorting technology is divided into positive isolation, negative isolation/untouched cell isolation, depletion, multi-step isolation and automated cell separation systems. In this review, we firstly give a brief introduction to the classification and application of magnetic cell sorting technology, then discuss several new techniques and challenges based on magnetic cell sorting in recent years, such as improving the sorting efficiency by improving the structure of magnetic materials and magnetic field structure. The necessity of biological evaluation of magnetic cell sorting products was emphatically analyzed. Through the biological evaluation, the advantages and disadvantages of magnetic cell sorting products can be understood, and the research and development ability could be improved. Therefore, 10 biological evaluation technical parameters related to magnetic cell sorting products were proposed: yield, purity, sterility, cytotoxicity, cell morphology, viability, light scattering characteristics of cells, fluorescent antibody labeling ability of cells, cell activation and cell proliferation. The 10 biological evaluation technical parameters play an important role in promoting the standardized application of magnetic cell sorting.